Project Summary ? Abstract Neuroscientists are getting close to building realistic bioengineered ex vivo human brain models by: (1) introducing perfusable vascular networks to maintain tissue viability and promote 3D brain model growth; (2) generating the full complement of currently missing cell types; (3) building particular brain regions and exploring specific input and output signals. The rapid development of these three areas of ex vivo brain modeling is likely to produce tractable new bioengineered tools for understanding functional interconnectivity of the human brain, dysfunction involved in many neurodegenerative diseases, and perhaps even certain molecular mechanisms underlying cognition. Despite this field's considerable scientific promise, advances in bioengineered human brain modeling research could also raise novel ethical concerns around the moral status of large, complex human brain models and the ethical boundaries that should exist when manipulating increasingly realistic bioengineered brain constructs. As researchers construct more realistic organoids that resemble human brains in vitro, it is critically important to understand what ethical boundaries may exist and where researchers and regulators should draw the line for research, both to reduce uncertainties over which projects to pursue in the lab and to address future concerns regulators and the public may harbor about whether this research, if left unexamined, could inadvertently undermine public trust in science. This proposed project will establish ongoing and proactive ethical discussions among ethicists and the neuroscientists involved with this cutting-edge work, with the ultimate goal of developing greater awareness, understanding, and ? beyond the duration of the project ? guidance for future management of ethical issues that may be unique to new areas of brain modeling research. This project will be a close partnership between ethicists and scientists, each informing the other through an unprecedented two-year process of joint deliberation.